Abstract
A number of 6-substituted-3(2H)-pyrid-azinones and the corresponding methyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate derivatives carrying the arylpiperazinyl structure present
in potent antinociceptive agents reported in the literature were synthesized. As part
of a programme a series of diverse arylpiperazine derivatives of ethyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate were prepared and tested for their in vivo analgesic and anti-inflammatory activity by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model,
respectively.
Side effects of the compounds were examined on gastric mucosa. None of the compounds
showed gastric ulcerogenic effect compared with reference non-steroidal anti-inflammatory
drugs (NSAIDs). On the basis of available data, the structure-activity relationship
in the series of ethyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate derivatives was also discussed. When compared to parent
6-sub-stituted-3(2H)-pyridazinones, the new ester derivatives, for example ethyl (6-4-[(2-fluoro)phenyl]piperazine-3(2H)-pyridazi-none-2-yl)acetate
exhibited better analgesic and anti-inflammatory activity and a lower ulcerogenic
effect.
Key words
Analgesics - Anti-inflammatory drugs - 3(2H)-Pyridazinone derivatives, analgesic activity,
antiinflammatory activity
